The HIV-1 envelope glycoproteins play a central role in virus entry into the host cell, in the induction of cytopathic effects, and in the elicitation of an immune response. The goal of this proposal is to understand the relationship between structural features of the HIV-1 envelop glycoproteins and the functions of these molecules during virus infection. The approach that will be taken is to create mutations in HIV-1 envelope glycoprotein regions previously implicated in function. Envelope glycoprotein mutants will be analyzed structurally and functionally with respect to syncytium formation, virus replication and induction of cytopathic effects. Structural studies will be complemented by studying accessibility of selected wild type and mutant envelope glycoprotein regions to monospecific or monoclonal antibodies.